Dataset Information

3D structural models of transmembrane proteins.

ABSTRACT: Transmembrane proteins are macromolecules implicated in major biological processes and diseases. Because of their specific neighborhood, few transmembrane protein structures are currently available. The building of structural models of transmembrane proteins is a major research area. Because of the lack of available 3D structures, automatic homology modeling is not an efficient way of proposing pertinent structural models. Hence, most of the structural models of transmembrane proteins are developed through a more complex protocol that comprises the use of secondary structure prediction to complete the comparative modeling process. Then, refinement and assessment steps are performed go often to a novel comparative modeling process. Nowadays, it is also possible to take attention to the helix-helix and helix-lipid interactions, and even build quaternary structures. In all cases, the most important factor when proceeding to correct structural models is taking the experimental data into account.

SUBMITTER: de Brevern AG

PROVIDER: S-EPMC3178832 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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3D structural models of transmembrane proteins.

de Brevern Alexandre G AG

Methods in molecular biology (Clifton, N.J.) 20100101

Transmembrane proteins are macromolecules implicated in major biological processes and diseases. Because of their specific neighborhood, few transmembrane protein structures are currently available. The building of structural models of transmembrane proteins is a major research area. Because of the lack of available 3D structures, automatic homology modeling is not an efficient way of proposing pertinent structural models. Hence, most of the structural models of transmembrane proteins are develo ...[more]

PMID: 20665277

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Project description:Proteins of the tetraspanin family contain four transmembrane domains (TM1-4) linked by two extracellular loops and a short intracellular loop, and have short intracellular N- and C-termini. While structure and function analysis of the larger extracellular loop has been performed, the organization and role of transmembrane domains have not been systematically assessed.Among 28 human tetraspanin proteins, the TM1-3 sequences display a distinct heptad repeat motif (abcdefg)n. In TM1, position a is occupied by structurally conserved bulky residues and position d contains highly conserved Asn and Gly residues. In TM2, position a is occupied by conserved small residues (Gly/Ala/Thr), and position d has a conserved Gly and two bulky aliphatic residues. In TM3, three a positions of the heptad repeat are filled by two leucines and a glutamate/glutamine residue, and two d positions are occupied by either Phe/Tyr or Val/Ile/Leu residues. No heptad motif is apparent in TM4 sequences. Mutations of conserved glycines in human CD9 (Gly25 and Gly32 in TM1; Gly67 and Gly74 in TM2) caused aggregation of mutant proteins inside the cell. Modeling of the TM1-TM2 interface in CD9, using a novel algorithm, predicts tight packing of conserved bulky residues against conserved Gly residues along the two helices. The homodimeric interface of CD9 was mapped, by disulfide cross-linking of single-cysteine mutants, to the vicinity of residues Leu14 and Phe17 in TM1 (positions g and c) and Gly77, Gly80 and Ala81 in TM2 (positions d, g and a, respectively). Mutations of a and d residues in both TM1 and TM2 (Gly25, Gly32, Gly67 and Gly74), involved in intramolecular TM1-TM2 interaction, also strongly diminished intermolecular interaction, as assessed by cross-linking of Cys80.Our results suggest that tetraspanin intra- and intermolecular interactions are mediated by conserved residues in adjacent, but distinct regions of TM1 and TM2. A key structural element that defines TM1-TM2 interaction in tetraspanins is the specific packing of bulky residues against small residues.

Dataset Information

3D structural models of transmembrane proteins.

Publications

3D structural models of transmembrane proteins.

Similar Datasets

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